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Introduction of d ‐Amino Acids in Minimalistic Peptide Substrates by an S ‐Adenosyl‐ l ‐Methionine Radical Epimerase
Author(s) -
Vagstad Anna L.,
Kuranaga Takefumi,
Püntener Salome,
Pattabiraman Vijaya R.,
Bode Jeffrey W.,
Piel Jörn
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201809508
Subject(s) - peptide , amino acid , methionine , chemistry , enzyme , epimer , stereochemistry , biochemistry
Post‐translational modifying enzymes from the S ‐adenosyl‐ l ‐methionine (AdoMet) radical superfamily garner attention due to their ability to accomplish challenging biochemical reactions. Among them, a family of AdoMet radical epimerases catalyze irreversible l ‐ to d ‐amino acid transformations of diverse residues, including 18 sites in the complex sponge‐derived polytheonamide toxins. Herein, the in vitro activity of the model epimerase OspD is reported and its catalytic mechanism and substrate flexibility is investigated. The wild‐type enzyme was capable of leader‐independent epimerization of not only the stand‐alone core peptide, but also truncated and cyclic core variants. Introduction of d ‐amino acids can drastically alter the stability, structure, and activity of peptides; thus, epimerases offer opportunities in peptide bioengineering.